The goals of this BCD award are to: 1) train Kathryn Richdale, OD MS as an interdisciplinary clinician- scientist and 2) further elucidate the structural and mechanical changes associated with presbyopia. One of the NIH's new Roadmap initiatives is to create interdisciplinary research teams that are more analytically sophisticated and will yield fresh and unexpected insights; this project will achieve that aim. A five-year career-development program is proposed, consisting of formal coursework and training in biomedical engineering, radiology, mathematics and computer-based image processing. There is still limited understanding of the ocular changes associatedwith presbyopia. Much of the previous work has focused on either the function of the lens or of the ciliary body, but has failed to provide a comprehensive view of the entire accommodative system. Previous research has been limited by the inability to visualize the internal structures of the human eye in vivo. Studies have been confounded by the use of animal models not entirely similar to humans; pharmacological agents known to affect the normal physiological response; post mortem changes inherent to the use of cadaveric eyes; and ex vivo work using non- physiological forces and discounting the role of the iris, vitreous, and choroid. Presbyopia may likely be a multifactorial process, as no one mechanism is able to explain the early onset, continued linear decline, and complete loss of function. In order to test hypotheses that would support the lenticular theory and/or the extra- lenticular theory of presbyopia, we will image and analyze the accommodative structures in vivo in a cohort of human adults, and determine how those structures change with age and accommodative effort. Eighty-five patients between the ages of 30 and 50 years will be enrolled. Optical coherence tomography, magnetic resonance imaging, and ultrasound-based techniques will be used to examine the crystalline lens, ciliary body, and geometric relationship of the structures. The accommodated and unaccommodated eye will be imaged, and the patient's accommodative response will be measured with auto-refraction and photorefraction. Computer-based image processing tools will be used to objectively analyze the images. The results will advance the understanding of the ocular changes associated with presbyopia and will allow for the development of future treatment options. RELEVANCE (See instructions): Presbyopia, a loss of focusing ability associated with the normal aging process, affects 100% of the population. A study of the structures of the eye associated with focusing is required to understand the changes involved in presbyopia and to advance the research of new treatment options.